Contents

Function

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun and stimulates CRE-dependent transcription. The protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. Additional transcript variants have been identified but their biological validity has not been determined.[1]

The gene atf2 is located at human chromosome 2q32.[2] The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton.[3] ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK.[4] ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol ester has been demonstrated.[5]

Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors.[6][7] ATF-2 may mediate oncogenesis caused by mutant Ras protein[8] and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells.
ATF2 has also been shown to be phosphorylated at its C-terminal (Serine 472 and 480 in mouse; Serine 490 and 498 in human) by ATM upon double-stranded breaks. Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.